We have been evaluating granulopoiesis in myeloproliferative and other hematologic disorders by utilizing in vitro marrow culture techniques. The marrow granulocytic colony-forming capacity (CFC), the proportion of granulocytic progenitor cells and DNA synthesis (GPC-S), and urinary and serum levels of colony stimulating factor (CSF) are being determined in order to evaluate the physiologic and pathogenetic relevance of these parameters. Our studies of patients with acute myeloid leukemia (AML) in remission indicates that large shifts in the proportions of GPC-S occur following pulses at chemotherapy. An acute decrease of GPC-S occurs during therapy following by a secondary overshoot 1-2 days after treatment, with a subsequent oscillatory return to basal level at 3-4 weeks. The initial increase of GPC-S is associated with elevations of urinary CSF output. GPC-S increases occurring when patients are treated with cycle active drugs appear to predict granulopoietic toxicity. These techniques, which evaluate the pattern of marrow granulopoietic response, are useful for assisting in devising chemotherapeutic regiments which may diminish granulopoietic toxicity. Studies with a patient with cycle neutropenia indicated that urinary CSF output was inversely related to the peripheral neutrophil count and directly related to marrow granulopoiesis. These data and the results of neutropenic plasma infusion suggest that this disease is due to decreased stem cell input into granulopoiesis. Serum and urine CSF levels are being evaluated in a variety of hematologic disorders. The albumin density gradient technique is prmving useful for distinctively characterizing populations of GPC. Our findings indicate that patients with leukemia or other myeloproliferative diseases have greater than 6% of GPC less dense than 1.062 g/cm3. This data is being used to further define the completeness of remissions and to characterize GPC in evolving myeloproliferative disorders. We plan to use this separation technique for evaluating the interaction between relatively homogeneous populations of GPC and CSF and oncogenic agents.